Treatment of Thrombotic Thrombocytopenic Purpura (TTP)
Initiate therapeutic plasma exchange (TPE) immediately upon clinical suspicion of TTP, combined with high-dose corticosteroids and rituximab, without waiting for ADAMTS13 results, as treatment delay directly increases mortality. 1, 2
Immediate Recognition and Diagnostic Confirmation
TTP diagnosis requires severe ADAMTS13 deficiency (<10% activity) combined with thrombocytopenia (typically <30,000/µL) and microangiopathic hemolytic anemia (MAHA), evidenced by schistocytes on peripheral smear, elevated LDH, decreased hemoglobin, and elevated indirect bilirubin. 1, 2
Order ADAMTS13 activity and inhibitor testing immediately, but do not delay treatment while awaiting results. 1 The PLASMIC score (≥5 points) identifies intermediate-to-high risk patients requiring immediate treatment in adults, incorporating platelet count <30,000/µL, hemolysis variables, absence of active cancer, absence of transplant, MCV <90 fL, INR <1.5, and creatinine <2.0 mg/dL. 1, 2
Coagulation studies (PT, aPTT, fibrinogen) should be normal or only mildly abnormal, distinguishing TTP from DIC. 1 Peripheral blood smear confirmation of schistocytes is critical. 2
First-Line Treatment Protocol
Therapeutic Plasma Exchange
Perform daily TPE using fresh frozen plasma, replacing 1-1.5 times the patient's plasma volume, until platelet count normalizes (≥150,000/µL). 1, 2, 3 This removes anti-ADAMTS13 autoantibodies and unusually large von Willebrand factor multimers while supplying deficient ADAMTS13. 3
Corticosteroids
Administer methylprednisolone 1 g IV daily for 3 days, with the first dose given immediately after the first TPE session. 1, 2 Following initial high-dose therapy, transition to prednisone 1-2 mg/kg/day. 2
Rituximab
Offer rituximab as part of initial therapy for acquired TTP and complete the full course if initiated. 1, 2 Rituximab targets ADAMTS13 autoantibodies and has become increasingly used in standard management, preventing 1-year relapses. 4, 5
Caplacizumab
Consider caplacizumab for patients with severe ADAMTS13 deficiency, particularly with elevated inhibitor levels or anti-ADAMTS13 IgG. 1, 2 This anti-von Willebrand factor antibody fragment inhibits the interaction between von Willebrand factor multimers and platelets, showing beneficial effects when added to standard treatment. 6 Discontinue caplacizumab if no exacerbation occurs within 3-5 days after stopping TPE. 2
Critical Management Pitfalls
Avoid platelet transfusions unless life-threatening hemorrhage occurs, as they may worsen thrombosis. 1, 2 Traditional anticoagulant and antiplatelet strategies are generally not effective in TTP despite the predominance of thrombotic manifestations. 7
Minimize RBC transfusion, targeting hemoglobin 7-8 g/dL in stable patients. 1, 2 Coordinate with the blood bank before any transfusions. 2
Monitoring During Active Treatment
Perform daily assessment of platelet count, hemoglobin, LDH, and clinical status during active TPE. 2 Continue weekly monitoring of hemoglobin levels until steroid taper is complete. 2
Refractory or Severe Disease
For patients not responding to standard therapy or presenting with life-threatening complications, consider additional immunosuppression including cyclosporine, cyclophosphamide, vincristine, mycophenolate mofetil, or anti-thymocyte globulin. 2 More intensive therapies such as twice-daily plasma exchange, pulses of cyclophosphamide or vincristine, or salvage splenectomy may be required. 5
Differential Diagnosis Considerations
ADAMTS13 activity >10% in a similar clinical context supports alternative diagnoses such as atypical hemolytic uremic syndrome (aHUS) or other thrombotic microangiopathies. 1 In patients with systemic lupus erythematosus presenting with thrombotic microangiopathy, complement-mediated TMA and antiphospholipid syndrome must be distinguished. 1, 2
Pediatric Considerations
In children, TTP is less common and plasma exchange can be deferred 24-48 hours until ADAMTS13 results confirm the diagnosis. 1